Hematopoietic stem cell transplantation is a mode of treatment which, after a malignant tumor has been destroyed by a pre-transplant regimen involving a combination of chemotherapy and radiotherapy, builds a new hematopoietic system by the transfusion of donor-derived or the patient's own hematopoietic stem cells. Of these, allogeneic hematopoietic stem cell transplantation involving the transplantation of donor-derived hematopoietic stem cells can be expected to have an anti-tumor effect, i.e., a graft-versus-tumor effect (also referred to below as the “GVT effect”), on various tumors of the hematopoietic system and solid tumors against which other therapeutic methods are likely to be ineffective. However, at the same time, there is a possibility that such therapy may be accompanied by graft-versus-host disease (also referred to below as “GVHD”) and by infections attributable to delayed immune reconstitution following transplantation. Such concerns have limited the expansion in the use of this approach as a cancer immunotherapy (Non-Patent Documents 1 and 2).
GVHD is a syndrome characterized by skin rash, jaundice and diarrhea, and is understood to arise from the infiltration of activated donor T-cells into, for example, the skin, liver and intestinal tract. With the appearance of immunosuppressants, which were rapidly developed starting in the late 1980s, the prevention of and treatment outcomes for GVHD improved significantly. At the same time, as a result of the decreased mortality from GVHD, lethal infections associated with immune deficiency following allogeneic hematopoietic stem cell transplantation emerged as a major factor affecting the prognosis of such transplantation. However, the pathogenic mechanism and effective treatments for delayed immune reconstitution following such transplantation have yet to be established. The situation is such that no alternative currently exists but to rely on symptomatic treatment involving the administration of immunoglobulin preparations and antibiotics.
The present invention sets out to employ a substance capable of depleting CD4 positive (also referred to below as CD4+) cells (which substance is also referred to below as a “CD4+ cell-depleting substance”) so as to promote immunological reconstitution or prevent infection following allogeneic hematopoietic stem cell transplantation. Such substances have not yet been reported in the literature.    Non-Patent Document 1: Shlomchik, W. D., Nature Reviews Immunology, 7(5), 340-352 (2007).    Non-Patent Document 2: Abrahamsen, I. W., and other 5 researchers., Haematologica, 90(1), 86-93 (2005).